The objectives of this proposal are to determine the structure-function relationship of specific salivary proteins which represent precursor constituents of the acquired enamel pellicle. The studies proposed will be carried out in a macaque animal model specifically developed for the purpose of conducting experiments which are ethically and technically unfeasible in human subjects. A proline-rich phosphoglycoprotein (MPRP) and a proline-rich phosphopeptide (M-statherin) have been isolated from the parotid secretion of the subhuman primate, Macaca fascicularis. The partial amino acid sequence of MPRP and the complete amino acid sequence of M-statherin have been determined and showed significant homology with the human proline-rich proteins (PRPs) and statherin, respectively. Both macaque proteins exhibit important biological functions. They are active inhibitors of both spontaneous precipitation of calcium phosphate salts and crystal growth in supersaturated solutions which has important implications for the maintenance and integrity of tooth surfaces. The specific aims of this project are (1) to determine the amino acid sequence and the carbohydrate structure of MPRP, (2) to elucidate and characterize the functional domains within MPRP and M-statherin with respect to their inhibition of spontaneous precipitation and crystal growth of calcium phosphate salts from supersaturated solutions and (3) to identify MPRP, M-statherin and characterize their derivatives in the in vivo formed acquired pellicle in order to understand their incorporation, survival and function in the oral environment. We propose to use the latest methodology for determining the covalent structure of MPRP such as automated Edman degradation and high resolution 1H-NMR spectroscopy. Well defined fragments will be assayed for function to identify the functional determinants within MPRP and M-statherin. Methods used for investigating the role of MPRP, M-statherin and their fragments in the natural acquired pellicle include radioisotope labeling of intact proteins and fragments, enzyme-linked immunosorbent assay (ELISA) and affinity chromatography. The achievement of the specific aims of this project will have a direct application to the understanding of the function of salivary proteins and pellicle constituents in the oral environment.